The goal of the proposed research is to understand how cell interactions contribute to the development of the nematode Caenorhabditis elegans. This study will use genetic, classical, and molecular methods to probe cell interactions at the single cell level. The research will focus on a set of cell interactions that are controlled by the homeotic gene lin-12. lin-12 is thought to be directly involved in cell communication: it encodes a protein that is probably located on the cell surface, and whose extracellular domain has sequence homology with mammalian LDL receptor and epidermal growth factor (EGF). Other genes that act in this process of cell interaction will be sought by identifying mutations that specifically suppress lin-12 defects, or by identifying mutations in other genes that cause lin-12 like phenotypes. Six such sup genes have already been identified. Loss-of-function mutations of the sup genes will be identified, and their effects on development studied. Temperature-shift experiments using temperature-sensitive mutants will define the time of gene action. Genetic mosaic analysis will determine in which cells the sup genes function. These results, together with epistasis interactions, will be used to infer a pathway of gene interactions. In corollary experiments, biochemical purification of the signal molecule used in one of the lin-12 controlled cell interactions will be attempted. From the analysis of the genetic pathway, key genes will be chosen to subject to molecular analysis. The ultimate goal will be to completely understand the role of these genes in mediating cell interaction. Study of cell interactions is directly relevant to an understanding of at least certain cancers. The intercellular growth signals PDGF, TGFa, and EGF (to which lin-12 is homologous) have been implicated in growth of cancer cells. Oncogenes themselves can encode mutant growth factors or receptors. Studies in C. elegans should provide important insights into the role of cell interactions in the regulation of growth and development.